DNA has the potential to provide clinically actionable information about a subject. For example, DNA from a tumor can reveal whether a cancer patient is in remission, or may inform a physician about immunotherapy treatments that may be effective for the patient. Similarly, fetal DNA can be studied to detect inherited genetic disorders, aneuploidy, or preeclampsia. However, a consistent challenge in accessing the actionable genetic information lies in existing approaches to sequencing DNA.
Typical DNA sequencing assays include the use of next-generation sequencing (NGS) platforms to capture, amplify, and sequence a subject's DNA. However, typical NGS platforms face a number of challenges. Detecting rare mutations such as a mutation in circulating tumor DNA in a plasma sample that also contains an abundance of “normal”, somatic DNA, requires successfully amplifying that tumor DNA for sequencing. Detecting structural alterations such as translocations, inversions, copy number variations, loss of heterozygosity, or large insertions or deletions (indels) is particularly difficult since NGS platforms give a large number of short reads for which assembly is made difficult by such structural alterations.